10-78037285-A-T

Variant names:

• chr10-78037285-A-T
• rs147128920
• NM_033022.4:c.371A>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_033022.4(RPS24):​c.371A>T​(p.Asn124Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,452,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N124S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: RPS24 NM_033022.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47
• Publications: 0 publications found

Genes affected

RPS24 (HGNC:10411): (ribosomal protein S24) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S24E family of ribosomal proteins. It is located in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Mutations in this gene result in Diamond-Blackfan anemia. [provided by RefSeq, Nov 2008]

RPS24 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Diamond-Blackfan anemia 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31755483).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033022.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS24	NM_033022.4	MANE Select	c.371A>T	p.Asn124Ile	missense	Exon 4 of 6	NP_148982.1
	RPS24	NM_001142285.2		c.371A>T	p.Asn124Ile	missense	Exon 4 of 5	NP_001135757.1
	RPS24	NM_001026.5		c.371A>T	p.Asn124Ile	missense	Exon 4 of 5	NP_001017.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS24	ENST00000372360.9	TSL:1 MANE Select	c.371A>T	p.Asn124Ile	missense	Exon 4 of 6	ENSP00000361435.4
	RPS24	ENST00000360830.9	TSL:1	c.371A>T	p.Asn124Ile	missense	Exon 4 of 7	ENSP00000354074.5
	RPS24	ENST00000435275.5	TSL:2	c.371A>T	p.Asn124Ile	missense	Exon 4 of 6	ENSP00000415549.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000551 AC: 8 AN: 1452046 Hom.: 0 Cov.: 31 AF XY: 0.00000555 AC XY: 4 AN XY: 721144

African (AFR) AF: 0.00 AC: 0 AN: 33290

American (AMR) AF: 0.00 AC: 0 AN: 43270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25886

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.00 AC: 0 AN: 84276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000723 AC: 8 AN: 1107122

Other (OTH) AF: 0.00 AC: 0 AN: 60102

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.0060	B
Vest4		0.54
MutPred		0.29		Gain of helix (P = 0.0143)
MVP		0.34
MPC		1.5
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.66
gMVP		0.49
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147128920; hg19: chr10-79797043;